Precision-based immuno-molecular augmentation (PBIMA) computerized system, method, and therapeutic vaccine

Abstract

As disclosed herein a precision based immunomolecular augmentation (PBIMA) high specificity patient profiling networked computer system, rapid therapeutic vaccine design method, and personalized vaccine, which utilizes immuno-molecular biopathway HLA affinity mapping and selection prediction ranking tools. This PBIMA approach comprises: Strategic-Selection, Molecular-Mapping, Antigen-Alignment, Receptor-Recognition, and Tactical Technology (SMART). The platform obtains data from a patient's genes and proteins as input. NGS data, including WES, WGS, ctDNA and cfDNA, RNAseq uses as input. PBIMA comprises a gene-protein-cell Cloud-based sequence editing interface to select the high confidence peptides. The PBIMA vaccine is a solution-based multi-purpose vaccine design strategy. PBIMA technology can produce therapeutic vaccines for cancer, autoimmune, neurodegenerative, inflammation-driven disease, and novel pathogen infection treatment. PBIMA therapeutic design is multi-mechanistic and broad-spectrum.

What is claimed is: 
     
       1. A precision-based immunomolecular augmentation (PBIMA) computerized method for designing and treating a patient with a customized therapeutic peptides or peptide vaccine, comprising:
 receiving a data input, by a cloud-based system, of a patient data comprising one or more of: a patient transcriptomics data, and a patient urine proteomics data; 
 computing a precision data output, by the cloud-based system, of a vaccine composition comprising a plurality of ranked peptide sequences encoding self-antigens and/or neo-antigens for a CD4+/CD8+ natural killer (NK) cell modulation specific to a patient's profile, and able to elicit an effective therapeutic response against a patient disease; 
 computing a CRISPR prime editing and an intracellular multi-core processing on the vaccine composition to produce a DNA-RNA and epigenetic modulation plurality of immunopeptide sequences; 
 conducting an immunopeptide synthesis and manufacturing of the vaccine composition; 
 conducting the delivery of the vaccine composition to a patient's clinician or institution, and administrating the vaccine composition to the patient; and 
 wherein the patient has been diagnosed with, and/or is genetically predisposed to one or more diseases comprising: a cancer, an autoimmune disease, a neurodegenerative disease, and/or a pathogenic infectious disease. 
 
     
     
       2. The PBIMA computerized method of  claim 1 , wherein computing a precision data output comprises one or more of:
 identifying a plurality of therapeutic peptides, peptide vaccine, self-antigens and neo-antigens for the CD4+/CD8+NK cell modulation from:
 a cancer patient genome; 
 a patient with an autoimmune disease; 
 a patient with a neurodegenerative disease, 
 a patient with a pathogenic infectious disease; 
 a patient's disease diagnostic reagents tagged with peptides; 
 
 ranking the plurality of therapeutic peptide sequences for the cloud-based system to use in the vaccine composition; and 
 wherein computing a CRISPR prime editing comprises the integration of PBIMA therapeutic vaccine ranked plurality of peptide sequences. 
 
     
     
       3. The PBIMA computerized method  claim 1 , further comprising: projecting a patient's OMICs data molecular profiling data onto a knowledgebase of one or more molecular interactions, functional associations, and mechanistic cancer models that have been compiled under different cancer hallmarks. 
     
     
       4. The PBIMA computerized method of  claim 1 , further comprising utilizing a programmed immunogenetic adaptation process knowledge for the patient's evolutionary regenerative adaptation or disease-free survival. 
     
     
       5. The PBIMA computerized method of  claim 1 , wherein the data analysis step further comprises one or more of: high-affinity profiling, matching and selecting of the plurality of peptide sequences based on a patient's immune compatibility, immune-editing ability, and adaptation process comprising system reproducibility, for treatment of a specific disease. 
     
     
       6. The PBIMA computerized method of  claim 1 , wherein a vaccine cost is controlled by increased precision of a peptide design, allowing for a smaller number of peptides in each vaccine or therapeutics. 
     
     
       7. The PBIMA computerized method of  claim 1 , further comprising a selection of a plurality of patients likely to respond to the vaccine composition using ex-vivo activation and expansion of a patient's T-cells. 
     
     
       8. The PBIMA computerized method of  claim 1 , wherein the vaccine composition comprises an efficacy of at least 60% for cancer or the disease that currently has no effective treatment or has been abandoned by standard-of-care and considered incurable. 
     
     
       9. The PBIMA computerized method of  claim 1 , wherein the cloud-based system comprises: a cloud-based server comprising one or more of a central processing unit (CPU) or a graphics processing engine (GPU); at least one application programming interface; and at least one online database; at least highest computing multi-core processor with at least a 96 cores. 
     
     
       10. The PBIMA computerized method of  claim 1 , further comprising conducting a genetic and protein analysis on a patient sample comprising one or more of: a fresh blood, a urine sample, a fresh tissue sample, or a stored tissue sample from a biobank. 
     
     
       11. A cloud-based computer system able to design a personalized peptide vaccine, comprising:
 a precision based immunomolecular augmentation (PBIMA) computing platform comprising a plurality of online databases and application program interfaces (APIs), and comprising non-transitory computer readable storage medium storing computer-executable code comprising all of:
 a next-generation sequencing (NGS) OMICS file processing unit comprising a Blood and RNA tumor VCF file, a WES VCF file, and a urine Proteomics data excel file; 
 a Peptide Analysis Tool comprising an open-source database and an online API 
 a Susceptibility Tool comprising an open-source database and an online API; 
 a Genome Uniqueness comprising an open-source database and an online API; 
 a Gene-Protein-Disease Interaction Database comprising an open-source or proprietary database and an online API; 
 a Sequence Integrity module comprising an open-source database and online API, Thermofisher, Dosorio R package); 
 PBIMA Unification API (Neo7Logix Cloud base integrative API) to design and rank neoantigens of the 9-aminoacid peptides-MHC-I, and 12-aminoacid peptides-MHC-II; 
 a Payload API to match the best payloads for delivery for a more specific targeted delivery; 
 
 a plurality of local and/or remote computers able to transmit patient input data to a PBIMA editing system, the input data comprising: NGS, WES, RNAseq, circulating DNA (ctDNA and cfDNA) and Urine proteomics data; 
 a wired and/or wireless network connecting local and/or remote computers' plurality; 
 wherein a patient has been diagnosed with, or is genetically predisposed to, a disease comprising: a cancer, an autoimmune disease, a neurodegenerative disease, or a pathogen related infectious disease; and 
 wherein the personalized peptide vaccine comprises a plurality of peptide sequences comprising about 5 to about 20 peptide sequences computed to be the most therapeutically effective peptide for treating the patient by eliciting a CD4+/CD8+NK cell modulation specific to a patient's profile. 
 
     
     
       12. The cloud-based system of  claim 11 , wherein the networked computer system's platform further comprises a gene-protein-cell communication network editing interface able to find one or more patient genetic mutations and predict a corresponding normal gene for the mutated genes in the patient. 
     
     
       13. A personalized peptide vaccine composition, comprising:
 a plurality of peptide sequences encoding self-antigens and neo-antigens for a CD4+/CD8+ Natural Killer (NK) cell modulation specific to a patient's profile, and able to elicit an effective therapeutic response against a patient disease; 
 wherein a patient has been diagnosed with, or is genetically predisposed to, a disease comprising: a cancer, an autoimmune disease, a neurodegenerative disease, or a pathogen related infectious disease; 
 wherein the plurality of peptide sequences comprises about 5 to about 20 peptide sequences computed to be the most therapeutically effective for treating the patient; and 
 wherein the individualized therapeutic peptides or peptide vaccine composition is produced by:
 receiving a data input, by a cloud-based system, of a patient data comprising one or more of: a patient transcriptomics data, and a patient urine proteomics data; 
 computing a precision data output, by the cloud-based system, of a vaccine composition comprising a plurality of therapeutic peptide sequences encoding peptides, self-antigens or neo-antigens specific to a patient's profile, and able to elicit an effective therapeutic response against a patient disease; 
 computing a CRISPR prime editing and an intracellular multi-core processing on the vaccine composition to produce a DNA-RNA and epigenetic modulation plurality of immunopeptide sequences; and 
 conducting an immunopeptide synthesis and manufacturing of the vaccine composition. 
 
 
     
     
       14. The personalized peptide vaccine composition of  claim 13 , further comprising a pharmaceutically acceptable carrier, comprising one or more of Citrullinated peptide, Cyclodextrin, poly I:C, Squalene or DHA, phosphatidylcholine, wherein the carrier is selected by utilizing a Payload application program interface (API) to determine the best candidate carrier comprising one or more adjuvants. 
     
     
       15. The vaccine composition of  claim 13 , wherein the cancer disease comprises one or more of: Multiple Myeloma, Melanoma, Breast Cancer, Colon Cancer, Lymphoma, Leukemia, Lymphoplasmacytic Lymphoma, Pancreatic Cancer, Lung Cancer, Bladder Cancer, Thyroid Cancer, and Brain Cancers. 
     
     
       16. The vaccine composition of  claim 13 , wherein the Autoimmune Disease comprises one or more of: Multiple Sclerosis (MS), Systemic Lupus Erythematosus (SLE), Amyotrophic Lateral Sclerosis (ALS), Scleroderma, Mixed Connective Tissue Disease, Hashimoto's Thyroiditis, Rheumatoid Arthritis and Autoimmune-Related Inflammation. 
     
     
       17. The vaccine composition of  claim 13 , wherein the Neurodegenerative Disease comprises one or more of: Alzheimer's Disease, Parkinson's Disease, Dementia, Brain Inflammatory Disease, CNS Degenerative Inflammation. 
     
     
       18. The vaccine composition of  claim 13 , wherein a pathogen-related infectious disease comprises one or more of: virus, bacteria, fungus, parasites with identified strains. 
     
     
       19. The vaccine composition of  claim 13 , comprising one or more sequences having at least 90% sequence identity with a polypeptide sequence of Table 5.